How does Serum Amyloid-P component contribute to the cognitive impairment observed in Alzheimer’s Disease? (360G-Wellcome-206954_Z_17_Z)

The neuropathology of Alzheimers Disease (AD) is associated with the formation of insoluble amyloid deposits containing fibres of amyloid-beta and tau protein. Despite this some patients exhibit high amyloid load yet little loss in cognitive performance. Recent studies have shown particular polymorphs of amyloid beta fibres are correlated with AD phenotypes, raising the possibility that factors that influence the dominant polymorph formed may determine the level of cognitive impairment experienced by the AD patient. Comparison of patients exhibiting similar amyloid load but significantly different cognitive outcomes have revealed that poor cognitive performance is associated with elevated levels of serum amyloid-P component (SAP) within the brain. Given SAPs role in the growth and persistence of amyloid deposits, this research project seeks to determine if SAP can influence the polymorph of amyloid-beta fibre formed, thereby influencing the level of cognitive impairment. To achieve this amyloid-beta fibres will be grown in with and without SAP, and the resulting fibres studies by solid-state magic-angle spinning to assess if the SAP has influenced the structure of the amyloid fibre formed. The data obtained will be compared with published data to assess if the structures formed can be related to particular AD phenotypes.